Scedosporium apiospermum and Lomentospora prolificans secrete siderophores (iron scavengers) during hyphal proliferation. Siderophores are virulence factors and potential clinical biomarkers of invasive scedosporiosis and lomentosporiosis. Both strains secreted a uniform spectrum of siderophores, including coprogen B (CopB), N α-methyl-coprogen B, dimethyl-coprogen, and ferricrocin, with N α-methyl-coprogen B being the fastest secreted and most abundant coprogen. Under iron and zinc restriction, reflecting a nutrient-limited host environment, L. prolificans secreted 45 times more CopB than did S. apiospermum, presumably contributing to its higher virulence. This robust mobilization of CopB was further enhanced by zinc surplus. Additionally, two novel cyclic peptides, Scedocyclin A and B, were characterized inScedosporium boydii using the de novo sequencing tool CycloBranch. Utilizing matrix-assisted laser desorption/ionization, the portfolio of coprogens detected had limits of detection and quantitation of 4.9 and 14.6 fmol/spot in complex matrices, respectively, making them strong candidates for the next-generation, routine diagnosis of invasive scedosporiosis and lomentosporiosis through the Biotyper siderotyping.

Department of Analytical Chemistry Faculty of Science Palacký University in Olomouc 17 listopadu 1192 12 779 00 Olomouc Czechia

Department of Bacteriology and Mycology National Reference Laboratory for Mycological Diagnostics Public Health Institute in Ostrava Partyzánské náměstí 2633 7 702 00 Ostrava Czechia

Department of Software Engineering Faculty of Information Technology Czech Technical University Prague Thákurova 9 160 00 Prague Czechia

Department of the Medical Microbiology second Faculty of Medicine Charles University and Motol University Hospital 5 Úvalu 84 150 06 Prague Czechia

Division of Infectious Diseases and Geographic Medicine Stanford University School of Medicine Foundation for Research in Infectious Diseases P O Box 2734 Saratoga California 95070 United States

Division of Parasitology and Mycology European Excellence Center in Medical Mycology National Reference Center on Chronic Aspergillosis Rennes University Hospital Inserm UMR_S 1085 Irset 2 Rue Henri le Guilloux 35033 Rennes France

Institute of Laboratory Medicine Faculty of Medicine University of Ostrava Syllabova 19 703 00 Ostrava Czechia

Laboratory of Molecular Structure Characterization Institute of Microbiology of the Czech Academy of Sciences Vídeňská 1083 142 00 Prague Czechia

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WHO fungal priority pathogens list to guide research, development and public health action. https://www.who.int/publications/i/item/9789240060241 (accessed Dec 9 , 2023).

Hoenigl M.; Salmanton-Garcia J.; Walsh T. J.; Nucci M.; Neoh C. F.; Jenks J. D.; Lackner M.; Sprute R.; Al-Hatmi A. M. S.; Bassetti M.; Carlesse F.; Freiberger T.; Koehler P.; Lehrnbecher T.; Kumar A.; Prattes J.; Richardson M.; Revankar S.; Slavin M. A.; Stemler J.; Spiess B.; Taj-Aldeen S. J.; Warris A.; Woo P. C. Y.; Young J. A. H.; Albus K.; Arenz D.; Arsic-Arsenijevic V.; Bouchara J. P.; Chinniah T. R.; Chowdhary A.; de Hoog G. S.; Dimopoulos G.; Duarte R. F.; Hamal P.; Meis J. F.; Mfinanga S.; Queiroz-Telles F.; Patterson T. F.; Rahav G.; Rogers T. R.; Rotstein C.; Wahyuningsih R.; Seidel D.; Cornely O. A. Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology. Lancet Infect. Dis. 2021, 21 (8), e246–e257. 10.1016/S1473-3099(20)30784-2. PubMed DOI

Ramirez-Garcia A.; Pellon A.; Rementeria A.; Buldain I.; Barreto-Bergter E.; Rollin-Pinheiro R.; de Meirelles J. V.; Xisto M.; Ranque S.; Havlicek V.; Vandeputte P.; Govic Y. L.; Bouchara J. P.; Giraud S.; Chen S.; Rainer J.; Alastruey-Izquierdo A.; Martin-Gomez M. T.; Lopez-Soria L. M.; Peman J.; Schwarz C.; Bernhardt A.; Tintelnot K.; Capilla J.; Martin-Vicente A.; Cano-Lira J.; Nagl M.; Lackner M.; Irinyi L.; Meyer W.; de Hoog S.; Hernando F. L. PubMed DOI

Mello T. P.; Oliveira S. S. C.; Branquinha M. H.; Santos A. L. S. Decoding the antifungal resistance mechanisms in biofilms of emerging, ubiquitous and multidrug-resistant species belonging to the PubMed DOI

Guegan H.; Poirier W.; Ravenel K.; Dion S.; Delabarre A.; Desvillechabrol D.; Pinson X.; Sergent O.; Gallais I.; Gangneux J. P.; Giraud S.; Gastebois A. Deciphering the role of PIG1 and DHN-melanin in PubMed DOI PMC

Mello T. P.; Bittencourt V. C. B.; Liporagi-Lopes L. C.; Aor A. C.; Branquinha M. H.; Santos A. L. S. Insights into the social life and obscure side of Scedosporium/Lomentospora species: ubiquitous, emerging and multidrug-resistant opportunistic pathogens. Fungal Bio. Rev. 2019, 33 (1), 16–46. 10.1016/j.fbr.2018.07.002. DOI

Toth E. J.; Nagy G. R.; Homa M.; Abrok M.; Kiss I. E.; Nagy G.; Bata-Csorgo Z.; Kemeny L.; Urban E.; Vagvolgyi C.; Papp T. Recurrent PubMed DOI PMC

Schwarz C.; Brandt C.; Antweiler E.; Krannich A.; Staab D.; Schmitt-Grohe S.; Fischer R.; Hartl D.; Thronicke A.; Tintelnot K. Prospective multicenter German study on pulmonary colonization with PubMed DOI PMC

Seidel D.; Meissner A.; Lackner M.; Piepenbrock E.; Salmanton-Garcia J.; Stecher M.; Mellinghoff S.; Hamprecht A.; Duran Graeff L.; Kohler P.; Cheng M. P.; Denis J.; Chedotal I.; Chander J.; Pakstis D. L.; Los-Arcos I.; Slavin M.; Montagna M. T.; Caggiano G.; Mares M.; Trauth J.; Aurbach U.; Vehreschild M.; Vehreschild J. J.; Duarte R. F.; Herbrecht R.; Wisplinghoff H.; Cornely O. A. Prognostic factors in 264 adults with invasive PubMed DOI

Sedlacek L.; Graf B.; Schwarz C.; Albert F.; Peter S.; Wurstl B.; Wagner S.; Klotz M.; Becker A.; Haase G.; Laniado G.; Kahl B.; Suerbaum S.; Seibold M.; Tintelnot K. Prevalence of PubMed DOI

Pham T.; Giraud S.; Schuliar G.; Rougeron A.; Bouchara J. P. Scedo-Select III: a new semi-selective culture medium for detection of the PubMed DOI

Gilgado F.; Cano J.; Gené J.; Guarro J. Molecular phylogeny of the PubMed DOI PMC

Mina S.; Staerck C.; Marot A.; Godon C.; Calenda A.; Bouchara J. P.; Fleury M. J. J. PubMed DOI

Martin-Souto L.; Buldain I.; Areitio M.; Aparicio-Fernandez L.; Antoran A.; Bouchara J. P.; Martin-Gomez M. T.; Rementeria A.; Hernando F. L.; Ramirez-Garcia A. ELISA test for the serological detection of PubMed DOI PMC

Pini P.; Venturelli C.; Girardis M.; Forghieri F.; Blasi E. Prognostic potential of the panfungal marker (1 → 3)-β-D-glucan in invasive mycoses patients. Mycopathologia 2019, 184 (1), 147–150. 10.1007/s11046-018-0282-5. PubMed DOI

Keller N. P. Fungal secondary metabolism: regulation, function and drug discovery. Nat. Rev. Microbiol. 2019, 17 (3), 167–180. 10.1038/s41579-018-0121-1. PubMed DOI PMC

Macheleidt J.; Mattern D. J.; Fischer J.; Netzker T.; Weber J.; Schroeckh V.; Valiante V.; Brakhage A. A. Regulation and role of fungal secondary metabolites. Annu. Rev. Genet. 2016, 50, 371–392. 10.1146/annurev-genet-120215-035203. PubMed DOI

Kriegl L.; Havlicek V.; Dichtl K.; Egger M.; Hoenigl M. Siderophores: a potential role as a diagnostic for invasive fungal disease. Curr. Opin. Infect. Dis. 2022, 35 (6), 485–492. 10.1097/QCO.0000000000000862. PubMed DOI

Happacher I.; Aguiar M.; Yap A.; Decristoforo C.; Haas H. Fungal siderophore metabolism with a focus on PubMed DOI PMC

Luptakova D.; Patil R. H.; Dobias R.; Stevens D. A.; Pluhacek T.; Palyzova A.; Kanova M.; Navratil M.; Vrba Z.; Hubacek P.; Havlicek V. Siderophore-based noninvasive differentiation of PubMed DOI PMC

Patil R. H.; Luptakova D.; Havlicek V. Infection metallomics for critical care in the post-COVID era. Mass Spectrom. Rev. 2023, 42 (4), 1221–1243. 10.1002/mas.21755. PubMed DOI

Bertrand S.; Larcher G.; Landreau A.; Richomme P.; Duval O.; Bouchara J. P. Hydroxamate siderophores of PubMed DOI

Bertrand S.; Bouchara J. P.; Venier M. C.; Richomme P.; Duval O.; Larcher G. N PubMed DOI

Bairwa G.; Hee Jung W.; Kronstad J. W. Iron acquisition in fungal pathogens of humans. Metallomics 2017, 9 (3), 215–227. 10.1039/C6MT00301J. PubMed DOI PMC

Le Govic Y.; Papon N.; Le Gal S.; Lelievre B.; Bouchara J. P.; Vandeputte P. Genomic organization and expression of iron metabolism genes in the emerging pathogenic mold PubMed DOI PMC

Le Govic Y.; Papon N.; Le Gal S.; Bouchara J. P.; Vandeputte P. Non-ribosomal peptide synthetase gene clusters in the human pathogenic fungus PubMed DOI PMC

Le Govic Y.; Havlicek V.; Capilla J.; Luptakova D.; Dumas D.; Papon N.; Le Gal S.; Bouchara J. P.; Vandeputte P. Synthesis of the hydroxamate siderophore N PubMed DOI PMC

Luo R.; Zimin A.; Workman R.; Fan Y.; Pertea G.; Grossman N.; Wear M. P.; Jia B.; Miller H.; Casadevall A.; Timp W.; Zhang S. X.; Salzberg S. L. First draft genome sequence of the pathogenic fungus PubMed DOI PMC

Misslinger M.; Hortschansky P.; Brakhage A. A.; Haas H. Fungal iron homeostasis with a focus on PubMed DOI

Liu H.; Gravelat F. N.; Chiang L. Y.; Chen D.; Vanier G.; Ejzykowicz D. E.; Ibrahim A. S.; Nierman W. C.; Sheppard D. C.; Filler S. G. PubMed DOI PMC

Yap A.; Volz R.; Paul S.; Moye-Rowley W. S.; Haas H. Regulation of high-affinity iron acquisition, including acquisition mediated by the iron permease FtrA, is coordinated by AtrR, SrbA, and SreA in PubMed DOI PMC

Pavlaskova K.; Nedved J.; Kuzma M.; Zabka M.; Sulc M.; Sklenar J.; Novak P.; Benada O.; Kofronova O.; Hajduch M.; Derrick P. J.; Lemr K.; Jegorov A.; Havlicek V. Characterization of pseudacyclins A–E, a suite of cyclic peptides produced by PubMed DOI

Krasny L.; Strohalm M.; Bouchara J. P.; Sulc M.; Lemr K.; Barreto-Bergter E.; Havlicek V. PubMed DOI

Novak J.; Lemr K.; Schug K. A.; Havlicek V. CycloBranch: PubMed DOI

Novak J.; Skriba A.; Havlicek V. CycloBranch 2: molecular formula annotations applied to imzML data sets in bimodal fusion and LC-MS data files. Anal. Chem. 2020, 92 (10), 6844–6849. 10.1021/acs.analchem.0c00170. PubMed DOI

Blin K.; Shaw S.; Augustijn H. E.; Reitz Z. L.; Biermann F.; Alanjary M.; Fetter A.; Terlouw B. R.; Metcalf W. W.; Helfrich E. J. N.; van Wezel G. P.; Medema M. H.; Weber T. antiSMASH 7.0: new and improved predictions for detection, regulation, chemical structures and visualisation. Nucleic Acids Res. 2023, 51 (W1), W46–W50. 10.1093/nar/gkad344. PubMed DOI PMC

Haas H. Iron—a key nexus in the virulence of PubMed DOI PMC

Altschul S. F.; Wootton J. C.; Gertz E. M.; Agarwala R.; Morgulis A.; Schaffer A. A.; Yu Y. K. Protein database searches using compositionally adjusted substitution matrices. FEBS J. 2005, 272 (20), 5101–5109. 10.1111/j.1742-4658.2005.04945.x. PubMed DOI PMC

Haas H. Molecular genetics of fungal siderophore biosynthesis and uptake: the role of siderophores in iron uptake and storage. Appl. Microbiol. Biotechnol. 2003, 62 (4), 316–330. 10.1007/s00253-003-1335-2. PubMed DOI

Breci L. A.; Tabb D. L.; Yates J. R. 3rd; Wysocki V. H. Cleavage N-terminal to proline: analysis of a database of peptide tandem mass spectra. Anal. Chem. 2003, 75 (9), 1963–1971. 10.1021/ac026359i. PubMed DOI

Savelieff M. G.; Pappalardo L. Novel cutting-edge metabolite-based diagnostic tools for aspergillosis. PLoS Pathog. 2017, 13 (9), e1006486 10.1371/journal.ppat.1006486. PubMed DOI PMC

Kostrzewa M. Application of the MALDI Biotyper to clinical microbiology: progress and potential. Expert Rev. Proteomics 2018, 15 (3), 193–202. 10.1080/14789450.2018.1438193. PubMed DOI